After screening a large number of chemicals that are either analogs of adenosine or analogs of S-adenosyl-L-homocysteine (AdoHcy) that are modified in the base, ribose, sulfur or the homocysteinyl moiety, two most promising inhibitors of AdoHcy hydrolase have been found. They are 3-deazaadenosine (deaza-Ado) and 5'-deoxy-5'(isobutylthio)-3-deaza-adenosine (deaza-SiBA). Deaza-Ado is unique in being both a substrate and inhibitor of AdoHcy hydrolase. Deaza-Ado and other purine analogs, such as Ara-A, are also irreversible inhibitors of AdoHcy hydrolase. Both deaza-Ado and deaza-SIBA exert a broad spectrum antiviral activity against RNA and DNA viruses, as well as being able to prevent cellular transformation induced by oncogenic viruses. Both chemicals exhibit antimalarial activity against Plasmodium falciparum in culture. Deaza-Ado is a potent inhibitor of chemotaxis by neutrophil leukocytes, and phagocytic function by macrophages. When administered in vivo to rats, deaza-Ado caused a marked inhibition in the methylation of liver lipids, with concomitant reduction in the urinary excretion of 3-methoxy-4-hydroxy-mandelic acid and creatine biosynthesis in the liver.